Acoustic detection of a usage of an injection device

ABSTRACT

Implementations of the present disclosure are directed to an injection device (102) including a medicament reservoir (103) configured to store a medicament to be expelled by the injection device (102), an acoustic source (122a, 122b, 122c, 122d, 200, 300, 400) configured to generate an acoustic signal including information indicative of an amount of the medicament stored in the medicament reservoir (103), the acoustic signal being transmitted to an external device (104) configured to process the acoustic signal and to extract injection device data.

This disclosure relates to detection of a usage of an injection device,and more particularly, to acoustic detection of a usage of an injectiondevice.

Electronic injection devices allow patients to safely administer amedicament, without the need for constant supervision by medical staff,while enabling transmission of treatment data to the medical staff.Treatment data is generally transmitted by electronic components thatare characterized by a “medium” or “typical” power consumption. Usually,electronic injection devices are powered by a battery integrated withinthe device or through wired connection by an external energy supply.Both integrated batteries and wired connections present severaldisadvantages. For example, current configurations of electronicinjection devices lead to idle drainage of the energy supply, such that,even if the electronic injection device has not been used, long shelflife can exhaust the life of the battery. A low battery condition canlead to no—or malfunction of the device, an incorrect dosage, a misseddosage, or it can even make the electronic injection device unusable bystopping the operation of the electronic components.

Implementations of the present disclosure include acoustic detectionmechanisms and systems configured for transmitting injection device datawith minimum energy consumption. In accordance with one aspect of thepresent disclosure, a medicament injection system includes an injectiondevice and an external device. The injection device includes amedicament reservoir configured to store a medicament to be expelled bythe injection device, and an acoustic source configured to generate anacoustic signal including information indicative of an amount of themedicament stored in the medicament reservoir. The external deviceincludes an acoustic receiver configured to record the acoustic signaland one or more processors configured to process the recorded acousticsignal and to generate injection device data based on the processedrecorded acoustic signal. The external device is configured to displayinformation based on the injection device data.

In some implementations, the acoustic source includes a moving elementand an inhibition element that produce the acoustic signal byinteracting with each other. In some implementations, the moving elementincludes at least one of a lever-type snapper, a dual-sided lever, aspring-powered element, a rotating cam and a rotating wheel includingmultiple indents. In some implementations, at least one of the movingelement and the inhibition element includes an arrangement of aplurality of materials to generate a sequence of a plurality offrequencies. In some implementations, at least one of the moving elementand the inhibition element includes a plurality of geometrical featuresto generate a sequence of a plurality of frequencies. In someimplementations, the sequence of a plurality of frequencies isassociated with an identifier of the injection device. In someimplementations, the acoustic source includes a vibrating elementconfigured to generate a reverberation within the acoustic signal. Insome implementations, the reverberation is associated with an identifierof the injection device. In some implementations, the acoustic source isenclosed within the injection device. In some implementations, a portionof a wall of the injection device that is proximal to the acousticsource defines an opening configured to enhance transmission of theacoustic signal. In some implementations, the opening is covered by asealing membrane. In some implementations, the acoustic source isattached to an exterior surface of the injection device. In someimplementations, the acoustic source is integrated into a dial grip togenerate an omnidirectional transmission of the acoustic signal.

In accordance with another aspect of the present disclosure, aninjection device includes a medicament reservoir configured to store amedicament to be expelled by the injection device, an acoustic sourceconfigured to generate an acoustic signal including informationindicative of an amount of the medicament stored in the medicamentreservoir, the acoustic signal being transmitted to an external deviceconfigured to process the acoustic signal and to extract injectiondevice data.

In accordance with another aspect of the present disclosure, amedicament injection system includes an injection device and an externaldevice. The injection device includes a medicament reservoir configuredto store a medicament to be expelled by the injection device, anacoustic source configured to generate an acoustic signal includinginformation indicative of an amount of the medicament stored in themedicament reservoir, an acoustic receiver configured to record theacoustic signal, a control logic configured to process the recordedacoustic signal and to generate an injection device signal based on theprocessed recorded acoustic signal, and an antenna configured totransmit the injection device signal. The external device includes areceiver configured to receive the injection device signal, and one ormore processors configured to process the injection device signal and togenerate injection device data based on the processed injection devicesignal. The external device is configured to display information basedon the injection device data.

It is appreciated that systems in accordance with the present disclosurecan include any combination of the aspects and features describedherein. That is to say that methods in accordance with the presentdisclosure are not limited to the combinations of aspects and featuresspecifically described herein, but also include any combination of theaspects and features provided.

The details of one or more embodiments of the present disclosure are setforth in the accompanying drawings and the description below. Otherfeatures and advantages of the present disclosure will be apparent fromthe description and drawings, and from the claims.

FIGS. 1A-1H are exploded views of examples of devices in accordance withthe present disclosure.

FIGS. 2A-2G are examples of acoustic mechanisms in accordance with thepresent disclosure.

FIGS. 3A-3I are examples of acoustic mechanisms in accordance with thepresent disclosure.

FIGS. 4A-4C are examples of acoustic mechanisms in accordance with thepresent disclosure.

FIGS. 5A-5D are block diagrams of example system components that canexecute implementations of the present disclosure.

FIG. 6 is a flowchart illustrating an example process that can beexecuted to perform operations of the present disclosure.

FIG. 7 is a schematic illustration of example computer systems that canbe used to execute implementations of the present disclosure.

Like reference symbols in the various drawings indicate like elements.

Implementations of the present disclosure are generally directed togenerating an acoustic signal associated with an operation of aninjection device and transmitting injection device data using minimalenergy. More particularly, implementations of the present disclosure aredirected to directly transmitting acoustic signals including injectiondevice data to an external device and, optionally, harvesting energy topower electronic components of the injection device to collect andtransmit additional injection device data.

Electronic components of an electronic injection device may drain thedevice's energy source even when the device is idle. Accordingly,collection, processing and transmission of injection device data can behindered by idle drained batteries. As described in further detailherein, implementations of the present disclosure address thischallenge. For example, the injection device can include mechanicalcomponents that generate acoustic signals associated with an operationof the injection device without a battery or any other type of electricenergy supply. Further, the injection device can include mechanicalcomponents and electronic components that operate by using energyharvested from the environment. The electronic components of theinjection device can be configured for low-power data processing anddata transmission. An injection device configured to operate without abattery typically has a low environmental footprint and can bemanufactured as a disposable item.

FIGS. 1A-1F depict example systems 100 that can be used to executeimplementations of the present disclosure. For example, the examplesystems 100 can be used for generating acoustic signals and, optionally,for harvesting energy to power electronic components of an injectiondevice 102 to collect and transmit RF signals including injection devicedata. In the depicted example, the example system 100 includes one ormore injection devices 102, an external device 104, a network 106 and aserver system 108.

The injection device 102 can be a pre-filled, disposable injection penor the injection device 102 can be a reusable injection pen. Theinjection device 102 can be configured to communicate with the externaldevice 104 (e.g., a smart phone configured to generate RF signals). Forexample, the injection device 102 can be configured to generate acousticsignals that can be detected by the external device 104. The acousticsignals can include a sound signal with a frequency within a frequencyrange perceptible by a microphone 131 of the external device 104 (e.g.,20 Hz to 20 kHz).

In some implementations, the injection device 102 can be configured toharvest energy from the external device 104 and to transmit injectiondevice data to the external device 104. Energy harvesting defines theprocess of wireless electrical charging of the injection device 102using the external device 104 or an external source as an energydistributor. The process of energy harvesting includes capturing RFsignals generated by the external device 104, converting the RF signalsto electric signals, and boosting the electric signals to feed one ormore components of the injection device with electric energy. Theinjection device 102 can transmit to the external device 104 operationaldata (e.g., date and time of start of usage of injection device 102 andsensor measurements) and corresponding treatment data (e.g., amount andtime of medicament dispense by the injection device 102). In someimplementations, the injection device 102 can be associated with anidentifier that is used by the external device 104 to uniquely identifythe injection device 102.

The injection device 102 can include a housing 110 and a needle assembly115. The housing 110 can be molded from a medical grade plastic materialsuch as a liquid crystal polymer cyclic olefin copolymer (COC),cyclo-olefin polymer (COP) or glass. The housing 110 can be configuredto be at least partially covered by a cap 119 during storage of theinjection device. The housing 110 can contain a medicament reservoir103, an electronic module 105, a stopper 107, a plunger rod 118, aplunger head 109, a bearing 111, a dial grip 112, a dosage window 114,an injection button 120, one or more acoustic sources 122 a, 122 b, 122c, 122 d and, optionally, an acoustic receiver 124.

The medicament reservoir 103 can be configured to contain a fluidmedicament. The medicament can include a pharmaceutical formulationcontaining at least one pharmaceutically active compound. The medicamentcan include insulin analogs, insulin derivatives, analgesics, hormones,beta agonists, corticosteroids, or a combination of any of theabove-mentioned drugs. The medicament reservoir 103 can be aconventional, generally cylindrical, disposable container like acartridge or a syringe used to package prepared fluids such asmedicaments, anesthetics and the like. The medicament reservoir 103 canbe provided with a pair of ends, one end having a pierceable membrane,which receives an inward end of needle 113 in a liquid tight sealingengagement and the other end, close to the dial grip 112, being open,such that the stopper 107 can slide through it and move towards a needle113 when dispensing the medicament.

A dose of the medicament contained in the medicament reservoir 103 canbe ejected from the injection device 102 by turning the dial grip 112,which actuates one of the acoustic sources 122 a, 122 b, 122 c, 122 d togenerate a mechanical click sound. The selected dose is displayed viadosage window 114, for instance in multiples of so-called InternationalUnits (IU), wherein one IU is the biological equivalent of about 45.5micrograms of pure crystalline medicament ( 1/22 mg). An example of aselected dose displayed in dosage window 114 may for instance be 30 IUs,as shown in FIG. 1 . The numbers displayed in dosage window 114 can beprinted on a sleeve that is contained in housing 110 and mechanicallyinteracts with a plunger head 109 that is fixed at the end of theplunger rod 118 and pushes the stopper 107 of the medicament reservoir103. In some implementations, the selected dose can be displayeddifferently, for instance by an electronic display (e.g., the dosagewindow 114 may take the form of an electronic display). The bearing 111can provide firm mounting to one or both ends of the plunger rod 118.

The plunger head 109 (e.g., a back end of the plunger) can be configuredto expel a portion of the fluid by displacing the stopper 107 containedwithin the medicament reservoir 103, such that a position of the stopper107 is associated with an amount of the fluid within the injectiondevice 102. The stopper 107 can be a flexible stopper, such as a rubberstopper. The stopper 107 can be of a sufficient length so that thestopper 107 is not ripped or twisted when being engaged by the plungerhead 109.

The needle assembly 115 includes a needle 113 that can be affixed to thehousing 110. The needle 113 can be covered by an inner needle cap 116and an outer needle cap 117, which in turn can be covered by a cap 119.When needle 113 is stuck into a skin portion of a patient, and theninjection button 120 is pushed, the medicament dose displayed in displaywindow 114 can be ejected from injection device 102. When the needle 113of injection device 102 remains for a certain time in the skin portionafter the injection button 120 is pushed, a high percentage of the dose(e.g., more than approximately 95%) is actually injected into thepatient's body. Ejection of the medicament dose can actuate one of theacoustic sources 122 a, 122 b, 122 c, 122 d to generate a mechanicalclick sound, which can be different from sounds produced when using dialgrip 112, which actuates a different one of the acoustic sources 122 a,122 b, 122 c, 122 d. Injection device 102 can be used for severalinjection processes until either medicament reservoir 103 is empty orthe expiration date of injection device 102 (e.g., 28 days after thefirst use) is reached.

Before using injection device 102 for the first time, it may benecessary to perform a priming operation to generate an acoustic signaland, optionally, to harvest energy from the external source and/or toremove air from medicament reservoir 103 and needle 113. For instance,the priming operation can include actuating acoustic sources 122 a, 122b, 122 c, 122 d turning the dial grip 112 to select one or two units ofmedicament and pressing injection button 120 while holding injectiondevice 102 with the needle 113 upwards. Turning the dial grip 112 cancause a mechanical click sound to provide acoustic feedback to a user.

Each of the acoustic sources 122 a, 122 b, 122 c, 122 d includes anacoustic mechanism configured to generate a unique acoustic signal, forexample with a unique frequency pattern that can be differentiated fromthe acoustic signal of other acoustic sources. The acoustic mechanismsof the acoustic sources 122 a, 122 b, 122 c, 122 d can include pressureelements (e.g., buttons), rotating elements (e.g., rotating knobs,rotating cams, or rotating wheels), inhibition elements (e.g.,protrusions), vibration elements, latching elements, flexible elements,swinging elements, attenuation elements, and other mechanical elements,as described in detail with reference to FIGS. 2-4 . The acousticsources 122 a, 122 b, 122 c, 122 d can be attached to or integratedwithin the injection device 102 at different locations.

For example, an acoustic source 122 a can be located within the housing110 near to a moving element, such as the plunger rod 118, the plungerhead 109, the bearing 111, the dial grip 112, the dosage window 114,and/or the injection button 120. As a further example, an acousticsource 122 b (e.g., a button) can be located on a section of the housing110 that is covered by the cap 119 when the cap is on and can beactivated during removal of the cap 119 or during recapping of theinjection device 102. As a further example, an acoustic source 122 c(e.g., a button or rotating knob) can be located on the surface of thehousing 110 at a location independent from other components to beactivated by a user of the injection device 102. The acoustic source 122c being located on the surface of the housing 110, is substantially notaffected by the body of the injection device 102 and is characterized byoptimal directionality (e.g., is transmitted equally in all directions).As a further example, an acoustic source 122 d (e.g., a button) can belocated on the cap 119 to generate an acoustic signal associated with aparticular tapping motion performed by a user of the injection device102.

In some implementations, as illustrated in FIG. 1A, the acoustic source122 a is completely covered by the walls of the housing 110 and theacoustic receiver 124 is near to (e.g., 1-10 mm away from) the acousticsource 122 a. The acoustic signal produced by the acoustic source 122 acovered by the walls of the housing 110 is attenuated by one or morecomponents of the injection device 102.

In some implementations, as illustrated in FIG. 1B, the walls of thehousing 110 can include an opening 110 a adjacent to the acoustic source122 a and the acoustic receiver 124 is near to (e.g., 1-10 mm away from)the acoustic source 122 a. The opening 110 a can have a diameter withinthe range from about 0.5 mm to about 9 mm. The acoustic signal producedadjacent to the opening 110 a is a directional signal that istransmitted without attenuation through the opening 110 a while beingattenuated in other directions that include transmission through thewalls of the housing 110.

In some implementations, as illustrated in FIG. 1C, the walls of thehousing 110 can include a plurality of openings 110 b, 110 c, 110 dadjacent to the acoustic source 122 a and the acoustic receiver 124 isnear to (e.g., 1-10 mm away from) the openings 110 b, 110 c, 110 d. Theopenings 110 b, 110 c, 110 d can have a small diameter (e.g., smallerthan 1 mm) that prevents any mechanical interference with the innercomponents of the injection device 102. For example, the openings 110 b,110 c, 110 d can have a diameter within the range from about 0.1 mm toabout 2 mm. The acoustic signal produced adjacent to the opening 110 ais a directional signal that is transmitted without attenuation throughthe openings 110 b, 110 c, 110 d while being attenuated in otherdirections that include transmission through the walls of the housing110.

In some implementations, as illustrated in FIGS. 1D and 1E, the walls ofthe housing 110 can include an opening 110 a covered by a thin membrane110 e (e.g., with a thickness smaller than about 1 mm) adjacent to theacoustic source 122 a and an acoustic receiver 124 near to (e.g., 1-40mm away from) the acoustic source 122 a. The membrane 110 e can beconfigured to transmit the acoustic signal substantially withoutattenuation (e.g., by decreasing the amplitude of the acoustic signalless than approximately 5%). The membrane 110 e can be configured toseal the opening 110 a by preventing contamination of and/orinterference with components of the injections device. The membrane 110e can have a diameter equal to or larger than the opening 110 a and canbe attached to the surface of the housing 110, such as a label (e.g.,FIG. 1D). The membrane 110 e can have a diameter equal to the opening110 a and can be fixed within the opening 110 a (e.g., FIG. 1E).

In some implementations, as illustrated in FIG. 1F, the acoustic source122 a is embedded within a portion of a wall of the housing 110 and theacoustic receiver 124 is near to (e.g., approximately 1 mm toapproximately 40 mm away from) the acoustic source 122 a. The acousticsignal produced by the acoustic source 122 a is embedded within thehousing 110 is a directional signal that is transmitted withoutattenuation in a forward direction while being attenuated in otherdirections that include transmission through the walls of the housing110. In some implementations, as illustrated in FIG. 1G, the acousticsource 122 a is directly attached to a portion of an inner wall of thehousing 110. The acoustic signal produced by the acoustic source 122 acovered by the walls of the housing 110 is attenuated by one or morecomponents of the injection device 102.

In some implementations, as illustrated in FIG. 1H, the acoustic source122 a is integrated within the dial grip 112 and the acoustic receiver124 is near (e.g., 1-40 mm away from) to the acoustic source 122 a. Thedamping effects of the acoustic signal produced by the acoustic source122 a embedded within the dial grip 112 can be minimized if the acousticsource 122 a is a mechanically decoupled part. The acoustic signalproduced by the acoustic source 122 a embedded within the dial grip 112is substantially omnidirectional. FIG. 1G illustrates the injectiondevice 102 without an acoustic receiver 124. However, it can beunderstood that any configuration of the acoustic source 122 a (asdescribed with reference to FIGS. 1A-1H) is possible without theacoustic receiver 124.

In some implementations, the acoustic signal generated by one of theacoustic sources 122 a, 122 b, 122 c, 122 d can initiate a communicationbetween the electronic module 105 and the external device 104. Theelectronic module 105 can be configured to perform and/or assist withone or more functions of the injection device 102 (e.g., the ejection ofthe medicament). The electronic module 105 can be molded within acomponent of the injection device 102 or attached to the injectiondevice 102. The electronic module 105 can include an electroniccomponent 126 and an antenna 128.

In some implementations, the electronic component 126 can include asensor configured to detect a signal including an indication ofmedicament amount associated with a function of the injection device 102and to generate a sensor signal based on the signal. The function caninclude an operation of the injection device associated with dispensinga medicament amount, such as a displacement of the plunger rod 118. Thesignal including the indication of medicament amount can include anelectric signal, an acoustic signal, a mechanical signal, and/or anoptical signal. For example, the sensor can be configured to generate anelectric signal that is proportionate to an amount of medicament storedin the medicament reservoir 103 or dispensed by the injection device102. Further, the sensor can include a mechanical component, an acousticcomponent (e.g., a piezo element), an optical component (e.g., pairs oflight emitting diodes and photodiodes), a magnetic component (e.g.,permanent magnet or plastic containing ferromagnetic particles), anelectric component (e.g., capacitive electrode, variable resistance),contact switches or a combination thereof. Further, the sensor caninclude an incremental dosing sensor configured to measure an amount ofexpelled medicament. In some implementations, the sensor can beconfigured to include in addition to the sensor configured to detect asignal indicating the amount of medicament an environmental sensor. Theenvironmental sensor can include any of a temperature sensor, a humiditysensor, an air quality sensor, or a light intensity sensor. In someimplementations, multiple sensors can be included in the injectiondevice 102 of FIG. 1 at different locations to detect medicament amountassociated data and/or to increase an accuracy of a result associatedwith the sensor measurements. The sensor can transmit a signal (e.g., avoltage) to the control component 124.

In some implementations, the electronic component 126 can include acontrol component, such as an ultra-low power (μW) platform chip,operating in a in a power range from tens of μW to nW. The controlcomponent can be configured to process the signal received from theacoustic sources 122 a, 122 b, 122 c, 122 d and to transmit injectiondevice data using the antenna 128. The antenna 128 can be a radiofrequency (RF) ultra-wide band or millimeter wave antenna that cantransmit injection device data to the external device 104, as describedwith reference to FIGS. 5A-5D. The antenna 128 can be electricallyinsulated from the surface of the injection device 128 to prevent a userinteraction from influencing the signal and signal strength. Thecommunication field 130 can enable communication between the injectiondevice 102 and the external device 104. The communication field 130 canbe based on an ultra-low power RF transmission protocol. The signalstransmitted by the antenna 128 of the injection device 102 can includethe amount of the fluid in the medicament reservoir 103, additionalenvironmental values, and the identifier of the injection device 102. Insome implementations, the electronic components of the electronic module105 can be integrated within the housing 110 at a single location or atmultiple locations (e.g., fitted within or attached to the plunger rod118, a cavity in the plunger head 109, a cavity in the stopper 107 or awall of the medicament reservoir 103). Further details regarding thecomponents and functionalities of the electronic module 105 are providedwith reference to FIGS. 5A-5D.

The external device 104 can communicate with the injection device 102over the communication field 130 and with one or more of the serverdevices 108 over the network 106. In some implementations, the externaldevice 104 can include any appropriate type of computing device such asa desktop computer, a laptop computer, a handheld computer, a tabletcomputer, a personal digital assistant (PDA), a cellular telephone, anetwork appliance, a camera, a smart phone, a smart watch, an enhancedgeneral packet radio service (EGPRS) mobile phone, a media player, anavigation device, an email device, a game console, or an appropriatecombination of any two or more of these devices or other data processingdevices.

The external device 104 can include a transceiver 132 (e.g., amicrophone and an antenna), a processor 134 and a display 136. Thetransceiver 132 can be configured to transmit signals to activate and/orpowers the injection device 102 and receive signals from the injectiondevice 102. The transceiver 132 can be configured to spontaneouslytransmit signals to the injection device 102 at a pre-set frequencyduring pre-set time intervals. The processor 134 can be configured toprocess the data transmitted by the injection device 102. The externaldevice 104 can be configured to enable a user to interact with thedisplay 136 (e.g., through a graphical user interface) to initiate acommunication between the external device 102 and the injection device102. The display 136 can be configured to display the data received fromthe injection device 102 and processed by the external processor 134.Further details regarding the components and functionalities of theexternal device 104 are provided with reference to FIGS. 5A-5D.

In some implementations, the server device 108 includes at least oneserver 138 and at least one data store 140. In the example of FIG. 1 ,the server device 108 is intended to represent various forms of serversincluding, but not limited to a web server, an application server, aproxy server, a network server, and/or a server pool. In general, serversystems accept requests for application services and provide suchservices to any number of client devices (e.g., the external device 104)over the network 106 to support monitoring of usage of the injectiondevice 102. In some implementations, a user (such as a patient or ahealthcare provider) can access the application services to analyze pastand present data associated with the usage of the injection device 102.The past and present data associated with the usage of the injectiondevice 102 can include dates of medicament injection, expelled doses perdate and remaining amount of medicament within the injection device 102.

FIGS. 2A-2G depict example acoustic mechanisms 200 that can be used toexecute implementations of the present disclosure. The example acousticmechanisms 200 are used for generating acoustic signals includinginjection device data. The example acoustic mechanisms 200 generate anacoustic signal through the mechanical interaction of a moving element202 a, 202 b, 202 c, 202 d, 202 e, 202 f, 202 g, with an inhibitionelement 204 a, 204 b, 204 c, 204 d, 204 e, 204 f, 204 g.

The moving element 202 a, 202 b, 202 c, 202 d, 202 e, 202 f, 202 g, canbe a portion of or an element attached to a plunger rod of an injectiondevice, such as plunger rod 118 described with reference to FIGS. 1A-1H.The moving element 202 a, 202 b, 202 c, 202 d, 202 e, 202 f, 202 g, canbe configured to perform an axial (longitudinal or transversal)displacement (FIGS. 2A-2D), a rotation (FIGS. 2E-2G) or a combination ofboth. The moving element 202 a, 202 b, 202 c, 202 d can include anobstacle 206 a, 206 b, 206 c, 206 d, 206 e, 206 f, 206 g. As illustratedin FIGS. 2A-2D, the obstacle 206 a, 206 b, 206 c, 206 d defines to aportion of the moving element 202 a, 202 b, 202 c, 202 d that includes avariation (increase or decrease) of the cross-sectional width of themoving element 202 a, 202 b, 202 c, 202 d relative to the beam width.The obstacle 206 a, 206 b, 206 c, 206 d can have a symmetric orasymmetric (sectioned) conical shape or (sectioned) pyramidal shape withsmooth or sharp edges. As illustrated in FIGS. 2E-2G, the obstacle 206e, 206 f, 206 g defines to a portion of the moving element 202 e, 202 f,202 g, that includes a variation (increase or decrease) of the radius ofthe moving element 202 e, 202 f, 202 g.

The inhibition element 204 a, 204 b, 204 c, 204 d, 204 e, 204 f, 204 gcan be a portion of or an element attached to a housing of an injectiondevice, such as housing 110 described with reference to FIGS. 1A-1H. Ina non-actuated state, the edges of the inhibition element 204 a, 204 b,204 c, 204 d, 204 e, 204 f, 204 g can be at a distance from the edges ofthe moving element 202 a, 202 b, 202 c, 202 d, 202 e, 202 f, 202 g. Inan actuated state (during a movement of moving element 202 a, 202 b, 202c, 202 d, 202 e, 202 f, 202 g), a portion of the inhibition element 204a, 204 b, 204 c, 204 d, 204 e, 204 f, 204 g touches a portion of themoving element 202 a, 202 b, 202 c, 202 d, 202 e, 202 f, 202 g. Theinhibition element 204 a, 204 b, 204 c, 204 d, 204 e, 204 f, 204 g caninclude a static portion (e.g., base of the inhibition element 204 a,204 b, 204 c, 204 d, 204 e, 204 f, 204 g) that is attached to a staticcomponent of an injection device (e.g., housing). The inhibition element204 a, 204 b, 204 c, 204 d, 204 e, 204 f, 204 g can include a movableportion (e.g., end of the inhibition element 204 a, 204 b, 204 c, 204 d,204 e, 204 f, 204 g) that is configured to move in response to amechanical collision with the corresponding moving element 202 a, 202 b,202 c, 202 d, 202 e, 202 f, 202 g. The inhibition element 204 a, 204 b,204 c, 204 d, 204 e, 204 f, 204 g can include a single sided leversnapper (FIGS. 2A, 2E, and 2F), a dual-sided lever (FIG. 2B), a springpowered element (FIG. 2C), a recessed lever (FIGS. 2D and 2G).

FIGS. 3A-3I depict example acoustic mechanisms 300 that can be used toexecute implementations of the present disclosure. The example acousticmechanisms 300 are used for generating acoustic signals with uniqueacoustic signatures associated with particular injection device data.The example acoustic mechanisms 300 generate an acoustic signal throughthe mechanical interaction of a moving element 302 a, 302 b, 302 c, 302d, 302 e, 302 f, 302 g, 302 h, 302 i with an inhibition element 304 a,304 b, 304 c, 304 d, 304 e, 304 f, 304 g, 304 h, 304 i. The acousticsignatures are generated by modifying one or more acoustic features ofthe moving element 302 a, 302 b, 302 c, 302 d, 302 e, 302 f, 302 g, 302h, 302 i or the inhibition element 304 a, 304 b, 304 c, 304 d, 304 e,304 f, 304 g, 304 h, 304 i.

The acoustic features can include geometrical features (e.g., FIGS. 3A,3E, 3G, 3H, and 3I), composition materials (e.g., FIGS. 3C and 3F),swinging elements (e.g., FIG. 3D), damping elements, flexible elements,single mode or multi-mode vibrating elements, number of moving elements302 a, 302 b, 302 c, 302 d, 302 e, 302 f, 302 g, 302 h, 302 i and/ornumber of inhibition element 304 a, 304 b, 304 c, 304 d, 304 e, 304 f,304 g, 304 h, 304 i. The geometrical features can include double- ormulti-click features (e.g., FIG. 3A), edge shapes (e.g., FIGS. 3E, 3G,and 3H), changes of dimensions (e.g., length, width, beam width,curvature, etc.), single split features, multiple split features (e.g.,FIG. 3I) or a combination of features.

The composition materials used to generate an acoustic signature caninclude different types of plastics, metals or a combination of both.For example, one or both of the moving element 302 a, 302 b, 302 c, 302d, 302 e, 302 f, 302 g, 302 h, 302 i and the corresponding inhibitionelement 304 a, 304 b, 304 c, 304 d, 304 e, 304 f, 304 g, 304 h, 304 ican be made of selected composition materials (e.g., FIG. 3C, 3E). Asanother example, one or both of the moving element 302 a, 302 b, 302 c,302 d, 302 e, 302 f, 302 g, 302 h, 302 i and the correspondinginhibition element 304 a, 304 b, 304 c, 304 d, 304 e, 304 f, 304 g, 304h, 304 i can be made of a first composition material and can include adeposition of a second material different from the first material (e.g.,printed ink or deposited metal) onto the first composition material(e.g., FIG. 3F).

As illustrated in FIG. 3B, the inhibition element 304 b can have apre-tension of a particular intensity, which generates an acousticsignal with a particular acoustic signature in response to collisionwith the obstacle of the moving element 302 b. As illustrated in FIG.3D, the use of a swinging element 306 d can dampen (e.g., attenuate) theacoustic signal or generate reverberations. In some implementations,particular types of composition materials are selected such thatacoustic attenuation can be frequency-dependent.

FIGS. 4A-4C depict example acoustic mechanisms 400 that can be used toexecute implementations of the present disclosure. The example acousticmechanisms 400 are used for time or frequency-domain encoding ofacoustic signals associated with a particular injection device data. Theexample acoustic mechanisms 400 generate an acoustic signal through themechanical interaction of a moving element 402 a, 402 b, 402 c with aninhibition element 404 a, 404 b, 404 c. The time-domain encoding or thefrequency-domain encoding can be generated by modifying one or moreacoustic features of the moving element 402 a, 402 b, 402 c or theinhibition element 404 a, 404 b, 404 c.

As illustrated in FIG. 4A, the moving element 402 a can be a rotatingwheel with multiple obstacles or indents of (two) different heights. Theheights can be selected such that during the rotation of the wheel, thelever 404 a can generate a click (e.g., an acoustic signal with a singlemaximum) at the interaction with the tall obstacles and not touch theshort obstacles. The distance between obstacles can be constant and thewidth of the obstacles can be constant, such that the height of theobstacles can be used as a binary value. The acoustic signal 406 aincludes a sequence of binary values that encodes in the time domain thedrug type and/or an identifier of the injection device.

As illustrated in FIG. 4B, the lever 404 b can have a sequentialdeposition of different materials within regions of different widths andthicknesses that are equidistant from each other. The type ofcomposition material used for a deposition segment corresponds to abinary value in the frequency domain. The interaction between the lever404 b and an obstacle 402 b, during the movement of either the lever 404b and/or the obstacle 402 b, generates an acoustic signal 406 b encodedin the frequency domain.

As illustrated in FIG. 4C, the obstacle 402 c can include a plurality ofvibrating elements that are equidistant from each other. The length of avibrating element dictates the resonance frequency corresponding to thatvibrating element. The interaction between the lever 404 c and anobstacle 402 c, during the movement of either the lever 404 c and/or theobstacle 402 c, generates an acoustic signal 406 c encoded in thefrequency domain.

FIGS. 5A-5D illustrate block diagrams of example systems 500 that canexecute implementations of the present disclosure. The system 500enables transmission of signals between an injection device 102 and anexternal device 104. In the example illustrated in FIG. 5A, theinjection device 102 includes an acoustic source 502. The acousticsource 502 is configured to generate acoustic signals encoding injectiondevice data, as described with reference to FIGS. 1-4 . The acousticsignals are generated by the acoustic source 502 within a rangedetectable by the external device 104. The external device 104 includesan in/out module 504 and a control module 506.

The in/out module 504 can be a standard component of the external device104 that is controlled by the control module 506 to supportcommunication with the injection device and the processing of theacoustic signals. The in/out module 504 includes a microphone 508, anaudio to digital (AD) converter 510, a display 512, a hardware driver514, and a memory 516. The display 512 can be configured to enable auser of the external device 104 to interact with the external device 104by providing user input and receiving indications associated with theinjection device 102 and the treatment performed using the injectiondevice 102. The hardware driver 514 includes a program that controls thedisplay 512. The memory 516 can be a computer-readable medium configuredto store data, including acoustic signals received by the microphone 508and results of processing the acoustic signals generated by the controlmodule 506.

The control module 506 can be an application downloadable from a serverthat is configured to control one or more operations of the externaldevice 104. For example, the operation of the external device 104 iscontrolled by programs executed by the control module 506. The controlmodule 506 includes an activation component 518, a detection component520, and an analysis component 522. The activation component 518 can beconfigured to generate an activation signal that can start acommunication process with the injection device 102, as described withreference to FIGS. 1A-1H. The activation of the communication process isan important factor contributing to the energy consumption of theexternal device 104, the usability and the reliability of the detectionin the proximity of the external device 104.

In some implementations, the activation signal is generated in responseto receiving a wake signal. The wake signal can include a word spoken bya user of the external device 104 or a specific acoustic noise generatedby an operation of the injection device 102 (e.g., a noise associatedwith a priming operation, a dose dialing click or a dispense click). Insome implementations, the activation signal is generated in response toreceiving a user input from the in/out module 504 that includes arequest to initiate the communication process with the injection device102. In some implementations, the activation signal is generated at apreset frequency (e.g., once or multiple times a day) that can beupdated by a user of the external device 104 to correspond with atreatment schedule. In some implementations, prior to activating thecommunication process, the activation component 518 provides a user ofthe external device 104, though the in/out module 504, with a messagerequesting approval to initiate the communication process with theinjection device 102.

The detection component 520 can be configured to generate a detectionsignal to control the detection of acoustic signals using the microphone508. In some implementations, the detection process can be controlledbased on one or more parameters of the activation process. For example,the detection component 520 can be configured to communicate with theactivation component 518 to initiate detection operations at aparticular time after the activation component 518 generated the triggersignal. The detection operations can include a pre-processing phase(e.g., normalization of the signal amplitude, stretching of the signalon the time scale, echo cancellation and/or reverberation suppression,removal of background noise, identifications of regions of interest), anactual detection phase, and a post-processing phase (e.g., data rangevalidation and/or plausibility checks). In some implementations, thedetection component 520 activates a filter (e.g., a bandpass filterand/or a band-reject filter) included in the external device 104 duringthe detection of the modulated RF signal.

The analysis component 522 can be configured to generate an analysissignal to control the analysis of the acoustic signals detected by themicrophone 508. For example, the analysis component 522 can control theselection of a signal processing algorithm used to process the acousticsignals and to generate an output data. The signal processing algorithmcan include one or a combination of basic signal processing methods(e.g., discrete Fourier transform, short-time Fourier transform,discrete cosine transform, discrete-time wavelet transform), short- andmid-term feature extraction, classifiers (e.g., k-nearest-neighborclassifier, decision tree, support vector machine, artificial neuralnetwork, deep neural network), algorithms based on a-priori knowledge ofthe expected signal to ‘train’ the algorithm and algorithms based ona-priori knowledge of the expected signal to correlate received signalswith expected signals to determine regions of interest. The output datacan include a number of clicks, a drug type along with the timestampavailable in the external device 104. The analysis component 522 cancontrol one or more operations performed on the output data by sendingit for storage to the memory 516, for display to the display component512, or to an antenna for upload to a server.

In the example illustrated in FIG. 5B, the injection device 102 is anelectromechanical device. The example injection device 102 of FIG. 5B isconfigured for ultra-low-power radio frequency (RF) communication, basedon ultra-wide band impulse radio (UWB IR) communication between theinjection device 102 and the external device 104. The example injectiondevice 102 of FIG. 5B, includes a plurality of electronic components andoptionally includes the acoustic source 502. The electronic componentsinclude an energy harvester 524, a controller 526, a transmitter 528, amemory 530, and a sensor 532. The harvester 524 can be configured forharvesting energy from the RF signals generated by the external device104. The harvester 524 can include an antenna configured to capture theRF signals, a piezoelectric crystal that generates an electrical pulsein response to receiving RF signals and a boost converter configured toincrease the voltage level for use by the controller 526. The controller526 can be a control component defining a junction point of theelectronic components of the injection device 102. The controller 526can process one or more signals received from the other electroniccomponents of injection device 102. The controller 526 can trigger ameasurement of the sensor 532 (e.g., a temperature sensor, a humiditysensor, and a fill level sensor). The controller 526 can transmit asignal to the transmitter 528 to trigger a transmission of data to theexternal device 104.

The memory 530 can include a microcontroller, a microprocessor or acombination of microprocessor components and other components formed ina single package. The memory 530 can be an arithmetic and/or a logicunit array. For example, the memory 530 can be configured to executeoperations on sensor data to generate output data. The memory 530 can beconfigured for low power consumption such that it can operate using theenergy supplied by the energy harvester 524. For example, the memory 530can include one or more of an electrically erasable programmableread-only memory (EEPROM), static random access memory (SRAM),ferroelectric random access memory (FRAM), magnetoresistive randomaccess memory (MRAM), and phase change memory (PCM). FRAM is anon-volatile random-access memory, which is based on the integration ofa ferroelectric material to achieve non-volatility. FRAM does notrequire a special sequence to write data nor does it require a chargepump to achieve the higher programming voltages (e.g., FRAM programs at1.5V). FRAM has the advantage of low power consumption (e.g., lower thanEEPROM), low write voltage requirements, fast write speeds and a largenumber of write-erase cycles. FRAM is compatible to standard CMOSprocesses, which means that it can be integrated with other logicfunctions into the injection device 102, by implementing additionalprocessing steps. MRAM provides fast read/write speeds in the order ofapproximately 35 ns, long data retention and an unlimited number ofread/write cycles. Reads of MRAM are not destructive.

The transmitter 528 can be configured to automatically transmit datausing UWB IR signals to the external device 104. In someimplementations, the transmission is performed automatically, inresponse to receiving an injection device data from the controller 526.The in/out module 504 of the external device 104 includes a receiver 534configured to detect signals transmitted by the injection device 102.The receiver 534 can include a microphone configured to detect acousticsignals generated by the acoustic source 502 and an ultra-wide bandreceiver configured to detect UWB IR signals generated by thetransmitter 528. The receiver 534 transmits the detected signals to thecontrol module 506, which processes the signals as described withreference to FIG. 5A.

In the example illustrated in FIG. 5C, the injection device 102 is anelectromechanical device. The example injection device 102 of FIG. 5C isconfigured for ultra-low-power RF communication, based on ultra-wideband impulse radio communication between the injection device 102 andthe external device 104. The example injection device 102 of FIG. 5C,includes a control module 536, a piezoelectric element 538, a sensor532, a battery, 540 and an antenna 542. The control module 536 includesa harvesting component 544, a controller 526, a clock 546, a transmitter528 and a memory 530.

The harvesting component 544 is configured to collect energy from one ormore external sources and convert the collected energy to electricalenergy. This energy may be stored or used directly to power otherelectronic components of the injection device 102. The harvestingcomponent 544 includes an interface to an energy source, an energyconverter, a DC/DC converter, and a load or a storage. Examples ofinterfaces include: an antenna designed for a specific frequencytogether with a matching network, a mechanical connection to a moveablemagnet or a piezo crystal, a mechanical connection to a piezo crystal,and a thermo-coupling to the heat source. The energy converter isconfigured to generate usable electrical energy from the energy source.Examples of energy converters include: a moving magnet that induces acurrent in a coil, a piezo crystal that generates an electrical pulse,and a charge pump that accumulates electrical charge.

The energy source can be associated with a user interaction with acomponent of the injection device 102. For example, the energy sourcecan be a mechanical energy generated by a user rotating a dialing knob,pressing a button, and removal or replacement of a cap. The motiongenerated by the user can be mechanically coupled to the energyconverter. The energy converter can be configured to use the torquedelivered by the user to generate electrical energy. In someimplementations, the energy converter can be attached to a spring thatcan store the mechanical energy generated by the interaction of the userand provide the stored energy upon request to the energy converter. TheDC/DC converter is configured to adjust the generated voltage to avoltage level suitable for the load, for example from 0.5V to 5V. Theload or storage can include a capacitor that provides a short-termstorage for the harvested energy. In some implementations, the load maybe directly attached to the DC/DC converter.

The sensor 532 can include one or more of multiple sensor types, such asa dialed dose sensor configured to generate an absolute value, a dosechange sensor configured to generate an incremental value, a dispenseddose sensor configured to generate an incremental value, and a dispensebutton sensor configured to generate a binary value (button pressed ornot pressed). The dialed dose sensor can be configured to trace arotation resistance. The dose change sensor can include a piezoelectricelement, a piezoelectric speaker, or a Wiegand sensor. The dose changesensor can be the piezoelectric element 538. The dose change sensor canbe configured to count the number of clicks within an acoustic signalgenerated by a user interacting with an acoustic element of theinjection device 102. The dispensed dose sensor can be configured todetect the dose based on an electrical contact.

The transmitter 528 is configured for generating UWB IR signals thatenable communications between the injection device 102 and the externaldevice 104. The UWB IR include very short RF pulses (e.g., smaller than1 ns) covering a large portion of the radio spectrum (e.g., bandwidthlarger than 500 MHz or 20% of the center frequency, whichever is lower),at a very low energy level. The operating frequency is chosen inaccordance with one or more national and federal regulations. Forexample, a frequency band with wide international acceptance is fromabout 6.5 GHz to about 8 GHz. In some implementations, the UWB IRsignals include a UWB IR standard widely accepted and available insmartphones from large vendors such that standard smartphone can be usedas the external device 104. In some implementations, the UWB IRcommunication includes a proprietary UWB protocol. The proprietary UWBprotocol uses an encoding, which consists of a combination of timemodulation, signal shape modulation, and amplitude modulation. Aproprietary UWB device (e.g. USB dongle for a smartphone) can be used asthe external device 104. The transmitter 528 generation of UWB IR istriggered by a user operation of the injection device 102 controlled bythe controller 526 based on time signals received from the clock 546.The clock can include one or more of mechanical resonant devices (e.g.,crystals and ceramic resonators) and electrical phase-shift circuits(e.g., resistor—capacitor oscillators and silicon oscillators).

The antenna 542 is configured for transmission of UWB IR signals. Theantenna 542 is configured such that the time characteristics UWB IR areconstant over the frequency spectrum, resulting in minimal pulsedistortion. The antenna 542 exhibits a flat frequency spectrum,resulting in wide pulses with minimal resonant distortion. The antenna542 is integrated into the injection device 102 near the surface of thehousing 110 to have minimal attenuation of the signal. The antenna 542is electrically insulated from the surface of the housing 110 to preventuser interaction from influencing the signal and signal strength.Possible implementations of the antenna 542 are the integration of achip antenna, or the integration of a conductive layer acting as theantenna on one of the plastic parts of the injection device 102. Theexternal device 104 can constantly or intermittently listen for incomingdata packets transmitted by the antenna 542. Depending on the detectionand storage concept, the transmission is performed once per injection,once per dose change or several times.

In the example illustrated in FIG. 5D, the injection device 102 is anelectromechanical device. The example injection device 102 of FIG. 5B isconfigured for millimeter wave radio frequency (mm Wave RF)communication with the external device 104. The example injection device102 of FIG. 5B, is a battery less device that includes a sensor 532, acontrol module 536, a receiving (RX) antenna 548, a transmitting (TX)antenna 550, and, optionally, the acoustic source 502. The controlmodule 536 includes a boost converter 554, an energy regulator 552, acontroller 526, a clock 546, and a RF generator 556.

The RX antenna 548 can be configured for harvesting energy from the RF(mm wave) signals generated by the transceiver 534 of the externaldevice 104 within a communication range larger than about 50 cm to about1 m. The operating frequency is chosen in accordance with one or morenational and federal regulations. For example, a frequency band withwide international acceptance is about 60 GHz. In some implementations,the RF (mm wave) signals include a RF (mm wave) standard widely acceptedand available in smartphones from large vendors such that standardsmartphone can be used as the external device 104. In someimplementations, the RF (mm wave) communication includes a proprietaryRF (mm wave) protocol. The proprietary RF (mm wave) protocol uses anencoding, which consists of a combination of time modulation, signalshape modulation, and amplitude modulation. A proprietary RF (mm wave)device (e.g. USB dongle for a smartphone) can be used as the externaldevice 104. The RX antenna 548 can include a very small (e.g., a fewmillimeters wide) antenna configured to capture the RF (mm wave)signals. The RX antenna 548 can be integrated into the injection device102 near the surface of the housing 110 to have minimal attenuation ofthe signal. The RX antenna 548 can be electrically insulated from thesurface of the housing 110 to prevent user interaction from influencingthe signal and signal strength. Possible implementations of the RXantenna 548 are the integration of a chip antenna, or the integration ofa conductive layer acting as the antenna on one of the plastic parts ofthe injection device 102. The energy captured by the RX antenna 548 istransmitted to the boost converted 554. The boost converted 554 isconfigured to boost the generated voltage to a voltage level suitablefor the energy regulator 552, which further provides regulated energy tothe controller 526.

The controller 526 can trigger a measurement of the sensor 532 (e.g., atemperature sensor, a humidity sensor, and a fill level sensor). Thecontroller 526 can transmit a sensor measurement to the RF generator 556to generate an RF (mm wave) signal based on the sensor measurement. Insome implementations, the generation of RF (mm wave) signals isperformed automatically, in response to receiving the sensor measurementfrom the controller 526. The RF (mm wave) signals are transmitted by theTX antenna 550 to the transceiver 534. The transceiver 534 can include amicrophone configured to detect acoustic signals generated by theacoustic source 502 and RF (mm wave) receiver configured to detect RF(mm wave) signals transmitted by the TX antenna 550. The transceiver 534transmits the detected signals to the control module 506, whichprocesses the signals as described with reference to FIGS. 5A-5C.

FIG. 6 is a flowchart illustrating an example process 600 that can beexecuted by devices and systems described with reference to FIGS. 1-5 .The process 600 begins by generating an acoustic signal using anacoustic source of an injection device (602). The acoustic signal can begenerating during an operation including a user actuating the acousticsource of the injection device. The acoustic sources can includepressure elements (e.g., buttons), rotating elements (e.g., rotatingknobs, rotating cams, or rotating wheels), inhibition elements (e.g.,protrusions), vibration elements, latching elements, flexible elements,swinging elements, attenuation elements, and other mechanical elements,as described in detail with reference to FIGS. 2-4 . The operation canbe a priming operation, a dose dispense operation, a cap removaloperation, a recapping operation, an on-off switch actuation or anyother type of operation including a transfer of a mechanical energythough an acoustic source. The acoustic signal can include multipleacoustic signals generated by multiple acoustic sources. For example,the acoustic signals can include data associated with an amount ofmedicament dispensed by the injection device, an amount of medicamentremaining in the medicament reservoir of the injection device, and/or anidentifier of the injection device. The acoustic signals can be encodedin time-domain or in the frequency-domain.

In response to generating the acoustic signal, a signal processingapplication is launched by the external device (604). The signalprocessing application can include a plurality of operations to beperformed by multiple components of the external device. The firstoperation of the signal processing application includes a pre-processingoperation (606). The pre-processing operation can include activation ofone or more filters to perform normalization of the signal amplitude,stretching of the signal on the time scale, echo cancellation and/orreverberation suppression, removal of background noise, and/oridentifications of regions of interest within the signal.

Further, it is determined, by the external device, whether the injectiondevice is a mechanical device including only mechanical components or anelectromechanical device including both mechanical components andelectronic components (608). In some implementations, the identifier ofthe injection device (included in the acoustic signal) indicates thetype of injection device. In some implementations, a user input on theexternal device indicates the type of the injection device.

If the injection device is an electromechanical device, the acousticsignal can be used as a trigger to initiate a communication between theinjection device and the external device (610). During establishedcommunication between the injection device and the external device, theinjection device can be configured to harvest energy from interrogationsignals transmitted by the external device. Harvesting energy caninclude generating, by a RF harvester, an electric signal based on anultra-wide band or millimeter wave RF signal received by an antenna ofthe injection device. In some implementations, the harvested energy isboosted for voltage increase. The electrical energy is used to power acontrol component configured control operation of other electroniccomponents. For example, the controller can determine whether thereceived electric energy is sufficient to activate one or moreadditional components of the injection device. If it is determined thatadditional energy is necessary, supplemental energy can be retrievedfrom one or more of a rechargeable battery, a capacitor and an energyharvester. Retrieving the supplemental energy can include harvestingenergy from additional sources different from the RF signal. Thesupplemental energy can be combined with the RF generated energy anddirected towards the controller. In response to determining that theenergy is sufficient, one or more additional components of the injectiondevice are activated to initiate sensor measurement. Sensor measurementscan include detection of an indication associated with a function of theinjection device to generate a sensor signal. The indication can includea mechanical signal, an acoustic signal, an optical signal, a magneticsignal, an electric signal, or a combination thereof generated before,during or after the function of the device. The function of theinjection device can include a movement of the plunger rod, adisplacement of the plunger head, a dose selection or other operationsassociated with dispensing of the medicament. The indication can beconverted by a sensor into a sensor signal. The controller can beconfigured to receive the sensor signal generated by the sensor. Thecontroller can process the sensor signal to generate injection devicedata (612). The injection device data can include acoustic signals,sensor signals from a plurality of sensors and additionally stored data.For example, the injection device data can include a unique identifierfor the injection device, an amount of administered medicament, anamount of medicament within a medicament reservoir, a medicamenttemperature, a timestamp of administering the medicament, a location,and/or a situation specific data for the injection device.

The injection device data can be transmitted, by the controller, to anRF generator to convert the data to an ultra-wide band or millimeterwave RF signal (614). It is determined whether the injection device hassufficient energy to power the antenna to transmit the RF signalassociated with the injection device data to the external device. If itis determined that additional energy is necessary, supplemental energycan be retrieved from one or more of the rechargeable battery, thecapacitor and the energy harvester. If it is determined that the antennahas sufficient energy, the antenna is powered and the ultra-wide band ormillimeter wave RF signal is transmitted to the external device (616).

In response to signal transmission, the signals generated by theinjection device are detected by the external device (618). For example,if the injection device is a mechanical device, the external devicedetects only acoustic signals. If the injection device is anelectromechanical device, the external device detects ultra-wide band ormillimeter wave RF signal and, optionally, additional acoustic signalstransmitted by the injection device. The detection operations caninclude recording of the detected signals transmitted by the injectiondevice. In some implementations, detection operations can includeapplying a filter (e.g., a bandpass filter and/or a band-reject filter)to the detected signal before recording the detected signal.

In response to signal detection, the signals are post-processed togenerate injection device results (620). Post-processing can includeoperations that integrate previously stored injection device data (e.g.,determining an amount of expelled medicament based on medicament volumecomparisons, determining a variation of treatment protocol), rangevalidation, and/or plausibility checks. The injection device results aredisplayed by a display of the external device (622). In someimplementations, if the injection device is an electromechanical device,in response to displaying the results, the communication between theinjection device and the external device is terminated.

FIG. 7 shows a schematic diagram of an example computing system 700. Thesystem 700 can be used for the operations described in association withthe implementations described herein. For example, the system 700 may beincluded in any or all of the server components discussed herein. Thesystem 700 includes a processor 710, a memory 720, a storage device 730,and an input/output device 770. Each of the components 710, 720, 730,and 770 are interconnected using a system bus 750. The processor 710 iscapable of processing instructions for execution within the system 700.In one implementation, the processor 710 is a single-threaded processor.In another implementation, the processor 710 is a multi-threadedprocessor. The processor 710 is capable of processing instructionsstored in the memory 720 or on the storage device 730 to displaygraphical information for a user interface on the input/output device770.

The memory 720 stores information within the system 700. In oneimplementation, the memory 720 is a computer-readable medium. In oneimplementation, the memory 720 is a volatile memory unit. In anotherimplementation, the memory 720 is a non-volatile memory unit. Thestorage device 730 is capable of providing mass storage for the system700. In one implementation, the storage device 730 is acomputer-readable medium. In various different implementations, thestorage device 730 may be a floppy disk device, a hard disk device, anoptical disk device, or a tape device. The input/output device 770provides input/output operations for the system 700. In oneimplementation, the input/output device 770 includes a keyboard and/orpointing device. In another implementation, the input/output device 770includes a display unit for displaying graphical user interfaces thatenable a user to access data related to an item that is collected,stored and queried as described with reference to FIGS. 1-6 .

The features described can be implemented in digital electroniccircuitry, or in computer hardware, firmware, software, or incombinations of them. The apparatus can be implemented in a computerprogram product tangibly embodied in an information carrier, e.g., in amachine-readable storage device, for execution by a programmableprocessor; and method steps can be performed by a programmable processorexecuting a program of instructions to perform functions of thedescribed implementations by operating on input data and generatingoutput. The described features can be implemented advantageously in oneor more computer programs that are executable on a programmable systemincluding at least one programmable processor coupled to receive dataand instructions from, and to transmit data and instructions to, a datastorage system, at least one input device, and at least one outputdevice. A computer program is a set of instructions that can be used,directly or indirectly, in a computer to perform a certain activity orbring about a certain result. A computer program can be written in anyform of programming language, including compiled or interpretedlanguages, and it can be deployed in any form, including as astand-alone program or as a module, component, subroutine, or other unitsuitable for use in a computing environment.

Suitable processors for the execution of a program of instructionsinclude, by way of example, both general and special purposemicroprocessors, and the sole processor or one of multiple processors ofany kind of computer. Generally, a processor will receive instructionsand data from a read-only memory or a random access memory or both. Theessential elements of a computer are a processor for executinginstructions and one or more memories for storing instructions and data.Generally, a computer will also include, or be operatively coupled tocommunicate with, one or more mass storage devices for storing datafiles; such devices include magnetic disks, such as internal hard disksand removable disks; magneto-optical disks; and optical disks. Storagedevices suitable for tangibly embodying computer program instructionsand data include all forms of non-volatile memory, including by way ofexample semiconductor memory devices, such as EPROM, EEPROM, and flashmemory devices; magnetic disks such as internal hard disks and removabledisks; magneto-optical disks; and CD-ROM and DVD-ROM disks. Theprocessor and the memory can be supplemented by, or incorporated in,ASICs (application-specific integrated circuits).

To provide for interaction with a user, the features can be implementedon a computer having a display device such as a OLED (organiclight-emitting diode) or LCD (liquid crystal display) monitor fordisplaying information to the user and a keyboard and a pointing devicesuch as a mouse or a trackball by which the user can provide input tothe computer.

The features can be implemented in a computer system that includes aback-end component, such as a data server, or that includes a middlewarecomponent, such as an application server or an Internet server, or thatincludes a front-end component, such as a client computer having agraphical user interface or an Internet browser, or any combination ofthem. The components of the system can be connected by any form ormedium of digital data communication such as a communication network.Examples of communication networks include, e.g., a LAN, a WAN, and thecomputers and networks forming the Internet.

The computer system can include clients and servers. A client and serverare generally remote from each other and typically interact through anetwork, such as the described one. The relationship of client andserver arises by virtue of computer programs running on the respectivecomputers and having a client-server relationship to each other.

In addition, the logic flows depicted in the figures do not require theparticular order shown, or sequential order, to achieve desirableresults. In addition, other steps may be provided, or steps may beeliminated, from the described flows, and other components may be addedto, or removed from, the described systems. Accordingly, otherimplementations are within the scope of the following claims.

The terms “drug” or “medicament” are used synonymously herein anddescribe a pharmaceutical formulation containing one or more activepharmaceutical ingredients or pharmaceutically acceptable salts orsolvates thereof, and optionally a pharmaceutically acceptable carrier.An active pharmaceutical ingredient (“API”), in the broadest terms, is achemical structure that has a biological effect on humans or animals. Inpharmacology, a drug or medicament is used in the treatment, cure,prevention, or diagnosis of disease or used to otherwise enhancephysical or mental well-being. A drug or medicament may be used for alimited duration, or on a regular basis for chronic disorders.

As described below, a drug or medicament can include at least one API,or combinations thereof, in various types of formulations, for thetreatment of one or more diseases. Examples of API may include smallmolecules having a molecular weight of 500 Da or less; polypeptides,peptides and proteins (e.g., hormones, growth factors, antibodies,antibody fragments, and enzymes); carbohydrates and polysaccharides; andnucleic acids, double or single stranded DNA (including naked and cDNA),RNA, antisense nucleic acids such as antisense DNA and RNA, smallinterfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleicacids may be incorporated into molecular delivery systems such asvectors, plasmids, or liposomes. Mixtures of one or more drugs are alsocontemplated.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other solidor flexible vessel configured to provide a suitable chamber for storage(e.g., short- or long-term storage) of one or more drugs. For example,in some instances, the chamber may be designed to store a drug for atleast one day (e.g., 1 to at least 30 days). In some instances, thechamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of thepharmaceutical formulation to-be-administered (e.g., an API and adiluent, or two different drugs) separately, one in each chamber. Insuch instances, the two chambers of the dual-chamber cartridge may beconfigured to allow mixing between the two or more components prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drugs or medicaments contained in the drug delivery devices asdescribed herein can be used for the treatment and/or prophylaxis ofmany different types of medical disorders. Examples of disordersinclude, e.g., diabetes mellitus or complications associated withdiabetes mellitus such as diabetic retinopathy, thromboembolismdisorders such as deep vein or pulmonary thromboembolism. Furtherexamples of disorders are acute coronary syndrome (ACS), angina,myocardial infarction, cancer, macular degeneration, inflammation, hayfever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs anddrugs are those as described in handbooks such as Rote Liste 2014, forexample, without limitation, main groups 12 (anti-diabetic drugs) or 86(oncology drugs), and Merck Index, 15th edition.

Examples of APIs for the treatment and/or prophylaxis of type 1 or type2 diabetes mellitus or complications associated with type 1 or type 2diabetes mellitus include an insulin, e.g., human insulin, or a humaninsulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1analogues or GLP-1 receptor agonists, or an analogue or derivativethereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or apharmaceutically acceptable salt or solvate thereof, or any mixturethereof. As used herein, the terms “analogue” and “derivative” refers toa polypeptide which has a molecular structure which formally can bederived from the structure of a naturally occurring peptide, for examplethat of human insulin, by deleting and/or exchanging at least one aminoacid residue occurring in the naturally occurring peptide and/or byadding at least one amino acid residue. The added and/or exchanged aminoacid residue can either be codable amino acid residues or othernaturally occurring residues or purely synthetic amino acid residues.Insulin analogues are also referred to as “insulin receptor ligands”. Inparticular, the term “derivative” refers to a polypeptide which has amolecular structure which formally can be derived from the structure ofa naturally occurring peptide, for example that of human insulin, inwhich one or more organic substituent (e.g. a fatty acid) is bound toone or more of the amino acids. Optionally, one or more amino acidsoccurring in the naturally occurring peptide may have been deletedand/or replaced by other amino acids, including non-codeable aminoacids, or amino acids, including non-codeable, have been added to thenaturally occurring peptide.

Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulinglulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28)human insulin (insulin aspart); human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Examples of insulin derivatives are, for example,B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®);B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin;B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 humaninsulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30)human insulin (insulin degludec, Tresiba®);B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, forexample, Lixisenatide (Lyxumia®), Exenatide (Exendin-4, Byetta®,Bydureon®, a 39 amino acid peptide which is produced by the salivaryglands of the Gila monster), Liraglutide (Victoza®), Semaglutide,Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®),rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3,GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen,Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701,MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030, CAM-2036, DA-15864,ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

An example of an oligonucleotide is, for example: mipomersen sodium(Kynamro®), a cholesterol-reducing antisense therapeutic for thetreatment of familial hypercholesterolemia.

Examples of DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Examples of hormones include hypophysis hormones or hypothalamushormones or regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Examples of polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)2 fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region. The term antibody also includes anantigen-binding molecule based on tetravalent bispecific tandemimmunoglobulins (TBTI) and/or a dual variable region antibody-likebinding protein having cross-over binding region orientation (CODV).

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific,tetraspecific and multispecific antibodies (e.g., diabodies, triabodies,tetrabodies), monovalent or multivalent antibody fragments such asbivalent, trivalent, tetravalent and multivalent antibodies, minibodies,chelating recombinant antibodies, tribodies or bibodies, intrabodies,nanobodies, small modular immunopharmaceuticals (SMIP), binding-domainimmunoglobulin fusion proteins, camelized antibodies, and VHH containingantibodies. Additional examples of antigen-binding antibody fragmentsare known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

Pharmaceutically acceptable salts of any API described herein are alsocontemplated for use in a drug or medicament in a drug delivery device.Pharmaceutically acceptable salts are for example acid addition saltsand basic salts.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the APIs, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentdisclosure, which encompass such modifications and any and allequivalents thereof.

A number of implementations of the present disclosure have beendescribed. Nevertheless, it will be understood that variousmodifications may be made without departing from the spirit and scope ofthe present disclosure. Accordingly, other implementations are withinthe scope of the following claims.

The invention claimed is:
 1. A medicament injection system comprising:an injection device comprising: a medicament reservoir configured tostore a medicament to be expelled by the injection device; an acousticsource configured to generate an acoustic signal comprising informationindicative of an amount of the medicament stored in the medicamentreservoir, wherein the acoustic signal includes an identifier of theinjection device, wherein the acoustic source includes a vibratingelement configured to generate reverberation within the acoustic signal,and wherein the reverberation is associated with the identifier of theinjection device; and an external device comprising: an acousticreceiver configured to record the acoustic signal; and one or moreprocessors configured to process the recorded acoustic signal and togenerate injection device data based on the processed recorded acousticsignal, wherein the external device is configured to use the identifierto uniquely identify the injection device and to display informationbased on the injection device data.
 2. The medicament injection systemof claim 1, wherein the acoustic source comprises a moving element andan inhibition element that produce the acoustic signal by interactingwith each other.
 3. The medicament injection system of claim 2, whereinthe moving element comprises at least one of a lever-type snapper, adual-sided lever, a spring-powered element, a rotating cam, and arotating wheel comprising multiple indents.
 4. The medicament injectionsystem of claim 2, wherein at least one of the moving element and theinhibition element comprises an arrangement of a plurality of materialsto generate a sequence of a plurality of frequencies.
 5. The medicamentinjection system of claim 2, wherein at least one of the moving elementand the inhibition element comprises a plurality of geometrical featuresto generate a sequence of a plurality of frequencies.
 6. The medicamentinjection system of claim 5, wherein the sequence of the plurality offrequencies is associated with the identifier of the injection device.7. The medicament injection system of claim 1, wherein the acousticsource is enclosed within the injection device.
 8. The medicamentinjection system of claim 1, wherein a portion of a wall of theinjection device that is proximal to the acoustic source defines anopening configured to enhance transmission of the acoustic signal. 9.The medicament injection system of claim 8, wherein the opening iscovered by a sealing membrane.
 10. The medicament injection system ofclaim 1, wherein the acoustic source is attached to an exterior surfaceof the injection device.
 11. The medicament injection system of claim 1,wherein the acoustic source is integrated into a dial grip to generatean omnidirectional transmission of the acoustic signal.
 12. An injectiondevice comprising: a medicament reservoir configured to store amedicament to be expelled by the injection device; an acoustic sourceconfigured to generate an acoustic signal comprising informationindicative of an amount of the medicament stored in the medicamentreservoir, wherein the acoustic signal includes an identifier of theinjection device, wherein the acoustic source includes a vibratingelement configured to generate reverberation within the acoustic signal,and wherein the reverberation is associated with the identifier of theinjection device; an acoustic receiver configured to record the acousticsignal; a control logic configured to process the recorded acousticsignal and to generate injection device data based on the processedrecorded acoustic signal; and an antenna configured to transmit theinjection device data to an external device that is configured to usethe identifier to uniquely identify the injection device and to displayinformation based on the injection device data.
 13. A medicamentinjection system comprising: an injection device comprising: amedicament reservoir configured to store a medicament to be expelled bythe injection device; an acoustic source configured to generate anacoustic signal comprising information indicative of an amount of themedicament stored in the medicament reservoir, wherein the acousticsignal includes an identifier of the injection device, wherein theacoustic source includes a vibrating element configured to generatereverberation within the acoustic signal, and wherein the reverberationis associated with the identifier of the injection device; an acousticreceiver configured to record the acoustic signal; a control logicconfigured to process the recorded acoustic signal and to generate aninjection device signal based on the processed recorded acoustic signal;and an antenna configured to transmit the injection device signal; andan external device comprising: a receiver configured to receive theinjection device signal; and one or more processors configured toprocess the injection device signal and to generate injection devicedata based on the processed injection device signal, wherein theexternal device is configured to use the identifier to uniquely identifythe injection device and to display information based on the injectiondevice data.